- Discovery of novel inhibitors of human phosphoglycerate dehydrogenase by activity-directed combinatorial chemical synthesis strategy
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Serine, the source of the one-carbon units essential for de novo purine and deoxythymidine synthesis plays a crucial role in the growth of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) which catalyzes the first, rate-limiting step in de novo serine biosynthesis has become a promising target for the cancer treatment. Here we identified H-G6 as a potential PHGDH inhibitor from the screening of an in-house small molecule library based on the enzymatic assay. We adopted activity-directed combinatorial chemical synthesis strategy to optimize this hit compound. Compound b36 was found to be the noncompetitive and the most promising one with IC50 values of 5.96 ± 0.61 μM against PHGDH. Compound b36 inhibited the proliferation of human breast cancer and ovarian cancer cells, reduced intracellular serine synthesis, damaged DNA synthesis, and induced cell cycle arrest. Collectively, our results suggest that b36 is a novel PHGDH inhibitor, which could be a promising modulator to reprogram the serine synthesis pathway and might be a potential anticancer lead worth further exploration.
- Gou, Kun,Luo, Youfu,Luo, Yuan,Sun, Qingxiang,Tan, Yuping,Tao, Lei,Zhao, Yinglan,Zhou, Xia,Zhou, Yue,Zuo, Zeping
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- RADIOACTIVE IODINE LABELED ORGANIC COMPOUND OR SALT THEREOF
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The present invention is a compound represented by the following formula (1) or a salt thereof. Furthermore, the present invention is an imaging agent used for imaging a tau protein, the imaging agent containing a compound represented by the formula (1) b
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Page/Page column 6
(2013/02/28)
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- CATALYTIC ARYLATION OF FURFURAL BY ARENEDIAZONIUM SALTS
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A series of 5-arylfurfurals were obtained by the reaction of furfural with arenediazonium chlorides in the presence of cupric chloride or ferrous chloride.The optimum reaction conditions depend on the nature of the substituent in the aromatic ring of the
- Obushak, N. D.,Lesyuk, A. I.,Ganushchak, N. I.,Mel'nik, G. M.,Zavalii, P. Yu.
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p. 2093 - 2097
(2007/10/02)
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